Stress: Ashwagandha

The roots of ashwagandha have long been used as “rasayana” drugs in Ayurvedic medicine to prevent or treat disease through the restoration of a healthy balance of life. Ashwagandha is used in Ayurvedic medicine as a general restorative medicine, and to improve general health, longevity, and prevent disease. Ashwagandha is much less stimulating than ginseng, making it preferable for patients with irritability, anxiety, and insomnia, and as a gentle tonic herb for the nervous system. The species name, somnifera, indicates the plant’s traditional use for sleep induction. Ashwagandha is immunomodu-latory and improves energy in patients experiencing stress-induced illness or exhaustion. It is indicated in inflammatory conditions, such as arthritis or other musculoskeletal disorders, and it is combined with other herbs in the treatment of cancer. Ashwagandha is used in Ayurveda and Unani systems of medicine for the treatment of pain, skin diseases, infection, inflammation, gastrointestinal disorders, rheumatism, and epilepsy. It is also used as a general tonic for the improvement of libido, liver health, mental state, cancer, heart disease, and the immune system. In vivo studies support its use for anti-inflammatory, immunomodulatory, antioxi-dant, thyroid stimulating, anxiolytic, stress-reduction, memory enhancing, and antineoplastic effects (Table Effects and Supposed Mechanisms of Some Actions of Ashwagandha). Ashwagandha is also reported to be hematopoietic, making it useful in the treatment of anemia. Ashwagandha is combined with levodopa, tropane alkaloid-containing plants, and other herbs as a therapy for Parkinsonism. Ashwagandha and other herbs may take the place of benzodiazepines and have a calming effect on the nervous system. Applications for ashwagandha based on traditional use, animal studies, and clinical evidence are listed in Box 6-4.

Effects and Supposed Mechanisms of Some Actions of Ashwagandha

EFFECTS SUPPOSED MECHANISM OF ACTION
Adaptogenic and immunomodulatory activity Steroidal lactones 5,20(R)-dihydroxy-6,7 alpha-epoxy-1-oxo-(5 alpha)-with a-2,24-dienolide and solasodine are known to possess adaptogenic and immunomodulating activity.
Anticonvulsant activity May be mediated via a GABA-ergic mechanism, likely through the barbiturate site on the macromolecule ionophore complex.
Anti-inflammatory effect May be mediated by decreased glycosaminoglycan synthesis. Ashwagandha extract increased phagocytosis and intracellular killing of peritoneal macrophages but did not increase the number of peripheral leukocytes.
Antistress / antianxiety effects Ashwagandha has demonstrated inhibition of stress-induced increases in dopaminergic receptor population in the corpus striatum. Ashwagandha may have a GABA-mimetic action.
Anticancer effects Withaferin A is the primary antineoplastic agent. Its mechanisms of action are still unclear. It has been found to arrest cellular division at metaphase, has shown inhibition of protein and nucleic acid syntheses in P388 cells in vitro, and RNA synthesis in Sarcoma 180 cells was inhibited. Withaferin A induces a G2 / M block. An immunostimulatory effect may be partially responsible for antineoplastic activity but this is uncertain, because in animal experiments withaferin A has shown both immunostimulatory and immunosuppressive activity. Some studies have focused on the ability to reduce stress-induced oxidative damage. Rat models have observed condensation and fragmentation of chromatin as quantitative markers, and other observable cellular changes to assess the cytoprotective properties of Withania. Such researchers propose that Withania extracts may help prevent free radical induced cleavage of DNA. Withania somnifera has been shown to increase the percentage of cells containing neurites in human neuroblastoma cells, promote the growth of new dendrites, may aid in the repair of damaged neuronal circuits. Withaferin is reported to have a radiosensitizing effect that has been noted in animal studies to reduce the toxicity of irradiation therapy, while improving the effects. Antitumor effects of Withania have also been investigated.
Memory-enhancing effects Withania appears to mediate stress-induced disruption of memory formation and retention. Neuroelectric, physical stress, and scopolamine induced disruption of acquisition and retention of memory consolidation all appear to be significantly reduced with the administration of Withania extracts. Animal experiments have noted Wthania to provide protection to neuronal cell bodies when animals are subjected to stressful conditions. Effects may also be due to increased cholinergic signal transduction cascade in the brain.
Sedative effects May be due to the alkaloid somniferum
Cardiovascular effects The steroidal lactones have a mild ionotropic and chronotropic effect on the heart.

Applications for Ashwagandha

  • Anxiety
  • Arthritis
  • Cancer (animal and in vitro data)
  • Cardiovascular effects (animal data)
  • Cyclophosphamide toxicity (animal data)
  • Debility
  • Epilepsy (animal data)
  • Growth and development
  • Immune system (animal data)
  • Infection (animal and in vitro data)
  • Inflammation (animal data)
  • Insomnia
  • Liver disease (animal data)
  • Memory (animal data)
  • Morphine withdrawal (animal data)
  • Muscle spasm (animal data)
  • Oxidation (animal data)
  • Pain (animal data)
  • Sedation (animal data)
  • Stamina (animal data)
  • Stress (animal data)
  • Thyroid stimulant (animal data)

Overall, toxicity studies have demonstrated a high level of safety of ashwagandha and its extracts. Safety is discussed further in Plant Profiles: Ashwagandha. The American Herbal Products Association has rated it a class 2b herb (not to be used during pregnancy); however, the evidence contraindicating its use during pregnancy is limited and questionable, and Ayurvedic practitioners have used it traditionally during pregnancy. Because ashwagandha reverses cyclophospha-mide-induced neutropenia, it may be prudent to avoid its use in patients with leukemia who are being treated with cyclophosphamide.